Comparative Study of the Impact of Human Leukocyte Antigens on Renal Transplant Survival in Andalusia and the United States.

Renal transplantation is the treatment of choice for patients suffering from chronic renal disease, one of the leading causes of death worldwide. Among the biological barriers that may increase the risk of acute renal graft rejection is the presence of human leukocyte antigen (HLA) incompatibilities between donor and recipient. This work presents a comparative study of the influence of HLA incompatibilities on renal transplantation survival in the Andalusian (South of Spain) and United States (US) population. The main objective is to analyse the extent to which results about the influence of different factors on renal graft survival can be generalised to different populations. The Kaplan-Meier estimator and the Cox model have been used to identify and quantify the impact on the survival probability of HLA incompatibilities, both in isolation and in conjunction with other factors associated with the donor and recipient. According to the results obtained, HLA incompatibilities considered in isolation have negligible impact on renal survival in the Andalusian population and a moderate impact in the US population. Grouping by HLA score presents some similarities for both populations, while the sum of all HLA scores (aHLA) only has an impact on the US population. Finally, the graft survival probability of the two populations differs when aHLA is considered in conjunction with blood type. The results suggest that the disparities in the renal graft survival probability between the two populations under study are due not only to biological and transplantation-associated factors, but also to social-health factors and ethnic heterogeneity between populations.

Special Issue "Body Sensors Networks for E-Health Applications".

Body Sensor Networks (BSN) have emerged as a particularization of Wireless Sensor Networks (WSN) in the context of body monitoring environments, closely linked to healthcare applications. These networks are made up of smart biomedical sensors that allow the monitoring of physiological parameters and serve as the basis for e-Health applications. This Special Issue collects some of the latest developments in the field of BSN related to new developments in biomedical sensor technologies, the design and experimental characterization of on-body/in-body antennas and new communication protocols for BSN, including some review studies.

Sensor Technologies to Manage the Physiological Traits of Chronic Pain: A Review.

Non-oncologic chronic pain is a common high-morbidity impairment worldwide and acknowledged as a condition with significant incidence on quality of life. Pain intensity is largely perceived as a subjective experience, what makes challenging its objective measurement. However, the physiological traces of pain make possible its correlation with vital signs, such as heart rate variability, skin conductance, electromyogram, etc., or health performance metrics derived from daily activity monitoring or facial expressions, which can be acquired with diverse sensor technologies and multisensory approaches. As the assessment and management of pain are essential issues for a wide range of clinical disorders and treatments, this paper reviews different sensor-based approaches applied to the objective evaluation of non-oncological chronic pain. The space of available technologies and resources aimed at pain assessment represent a diversified set of alternatives that can be exploited to address the multidimensional nature of pain.

Smart Bioimpedance Spectroscopy Device for Body Composition Estimation.

The purpose of this work is to describe a first approach to a smart bioimpedance spectroscopy device for its application to the estimation of body composition. The proposed device is capable of carrying out bioimpedance measurements in multiple configurable frequencies, processing the data to obtain the modulus and the bioimpedance phase in each of the frequencies, and transmitting the processed information wirelessly. Another novelty of this work is a new algorithm for the identification of Cole model parameters, which is the basis of body composition estimation through bioimpedance spectroscopy analysis. Against other proposals, the main advantages of the proposed method are its robustness against parasitic effects by employing an extended version of Cole model with phase delay and three dispersions, its simplicity and low computational load. The results obtained in a validation study with respiratory patients show the accuracy and feasibility of the proposed technology for bioimpedance measurements. The precision and validity of the algorithm was also proven in a validation study with peritoneal dialysis patients. The proposed method was the most accurate compared with other existing algorithms. Moreover, in those cases affected by parasitic effects the proposed algorithm provided better approximations to the bioimpedance values than a reference device.

Lessons Learned about the Design and Active Characterization of On-Body Antennas in the 2.4 GHz Frequency Band.

This work addresses the design and experimental characterization of on-body antennas, which play an essential role within Body Sensor Networks. Four antenna designs were selected from a set of eighteen antenna choices and finally implemented for both passive and active measurements. The issues raised during the process of this work (requirements study, technology selection, development and optimization of antennas, impedance matching, unbalanced to balanced transformation, passive and active characterization, off-body and on-body configurations, etc.) were studied and solved, driving a methodology for the characterization of on-body antennas, including transceiver effects. Despite the influence of the body, the antennas showed appropriate results for an in-door environment. Another novelty is the proposal and validation of a phantom to emulate human experimentation. The differences between experimental and simulated results highlight a set of circumstances to be taken into account during the design process of an on-body antenna: more comprehensive simulation schemes to take into account the hardware effects and a custom design process that considers the application for which the device will be used, as well as the effects that can be caused by the human body.

Smart Vest for Respiratory Rate Monitoring of COPD Patients Based on Non-Contact Capacitive Sensing.

In this paper, a first approach to the design of a portable device for non-contact monitoring of respiratory rate by capacitive sensing is presented. The sensing system is integrated into a smart vest for an untethered, low-cost and comfortable breathing monitoring of Chronic Obstructive Pulmonary Disease (COPD) patients during the rest period between respiratory rehabilitation exercises at home. To provide an extensible solution to the remote monitoring using this sensor and other devices, the design and preliminary development of an e-Health platform based on the Internet of Medical Things (IoMT) paradigm is also presented. In order to validate the proposed solution, two quasi-experimental studies have been developed, comparing the estimations with respect to the golden standard. In a first study with healthy subjects, the mean value of the respiratory rate error, the standard deviation of the error and the correlation coefficient were 0.01 breaths per minute (bpm), 0.97 bpm and 0.995 (p < 0.00001), respectively. In a second study with COPD patients, the values were −0.14 bpm, 0.28 bpm and 0.9988 (p < 0.0000001), respectively. The results for the rest period show the technical and functional feasibility of the prototype and serve as a preliminary validation of the device for respiratory rate monitoring of patients with COPD.

Inhibition of Gsk3b Reduces Nfkb1 Signaling and Rescues Synaptic Activity to Improve the Rett Syndrome Phenotype in Mecp2-Knockout Mice.

Rett syndrome (RTT) is the second leading cause of mental impairment in girls and is currently untreatable. RTT is caused, in more than 95% of cases, by loss-of-function mutations in the methyl CpG-binding protein 2 gene (MeCP2). We propose here a molecular target involved in RTT: the glycogen synthase kinase-3b (Gsk3b) pathway. Gsk3b activity is deregulated in Mecp2-knockout (KO) mice models, and SB216763, a specific inhibitor, is able to alleviate the clinical symptoms with consequences at the molecular and cellular levels. In vivo, inhibition of Gsk3b prolongs the lifespan of Mecp2-KO mice and reduces motor deficits. At the molecular level, SB216763 rescues dendritic networks and spine density, while inducing changes in the properties of excitatory synapses. Gsk3b inhibition can also decrease the nuclear activity of the Nfkb1 pathway and neuroinflammation. Altogether, our findings indicate that Mecp2 deficiency in the RTT mouse model is partially rescued following treatment with SB216763.

A Parametric Computational Analysis Into Galvanic Coupling Intrabody Communication.

Intrabody Communication (IBC) uses the human body tissues as transmission media for electrical signals to interconnect personal health devices in wireless body area networks. The main goal of this work is to conduct a computational analysis covering some bioelectric issues that still have not been fully explained, such as the modeling of skin-electrode impedance, the differences associated with the use of constant voltage, or current excitation modes, or the influence on attenuation of the subject's anthropometrical and bioelectric properties. With this aim, a computational finite element model has been developed, allowing the IBC channel attenuation as well as the electric field and current density through arm tissues to be computed as a function of these parameters. As a conclusion, this parametric analysis has in turn permitted us to disclose some knowledge about the causes and effects of the above-mentioned issues, thus, explaining and complementing previous results reported in the literature.

Bromodomain inhibition shows antitumoral activity in mice and human luminal breast cancer.

BET bromodomain inhibitors, which have an antitumoral effect against various solid cancer tumor types, have not been studied in detail in luminal breast cancer, despite the prevalence of this subtype of mammary malignancy. Here we demonstrate that the BET bromodomain inhibitor JQ1 exerts growth-inhibitory activity in human luminal breast cancer cell lines associated with a depletion of the C-MYC oncogene, but does not alter the expression levels of the BRD4 bromodomain protein. Interestingly, expression microarray analyses indicate that, upon JQ1 administration, the antitumoral phenotype also involves downregulation of relevant breast cancer oncogenes such as the Breast Carcinoma-Amplified Sequence 1 (BCAS1) and the PDZ Domain-Containing 1 (PDZK1). We have also applied these in vitro findings in an in vivo model by studying a transgenic mouse model representing the luminal B subtype of breast cancer, the MMTV-PyMT, in which the mouse mammary tumor virus promoter is used to drive the expression of the polyoma virus middle T-antigen to the mammary gland. We have observed that the use of the BET bromodomain inhibitor for the treatment of established breast neoplasms developed in the MMTV-PyMT model shows antitumor potential. Most importantly, if JQ1 is given before the expected time of tumor detection in the MMTV-PyMT mice, it retards the onset of the disease and increases the survival of these animals. Thus, our findings indicate that the use of bromodomain inhibitors is of great potential in the treatment of luminal breast cancer and merits further investigation.

Whole exome sequencing of Rett syndrome-like patients reveals the mutational diversity of the clinical phenotype.

Classical Rett syndrome (RTT) is a neurodevelopmental disorder where most of cases carry MECP2 mutations. Atypical RTT variants involve mutations in CDKL5 and FOXG1. However, a subset of RTT patients remains that do not carry any mutation in the described genes. Whole exome sequencing was carried out in a cohort of 21 female probands with clinical features overlapping with those of RTT, but without mutations in the customarily studied genes. Candidates were functionally validated by assessing the appearance of a neurological phenotype in Caenorhabditis elegans upon disruption of the corresponding ortholog gene. We detected pathogenic variants that accounted for the RTT-like phenotype in 14 (66.6 %) patients. Five patients were carriers of mutations in genes already known to be associated with other syndromic neurodevelopmental disorders. We determined that the other patients harbored mutations in genes that have not previously been linked to RTT or other neurodevelopmental syndromes, such as the ankyrin repeat containing protein ANKRD31 or the neuronal acetylcholine receptor subunit alpha-5 (CHRNA5). Furthermore, worm assays demonstrated that mutations in the studied candidate genes caused locomotion defects. Our findings indicate that mutations in a variety of genes contribute to the development of RTT-like phenotypes.

A Machine-to-Machine protocol benchmark for eHealth applications - Use case: Respiratory rehabilitation.

BACKGROUND: M2M (Machine-to-Machine) communications represent one of the main pillars of the new paradigm of the Internet of Things (IoT), and is making possible new opportunities for the eHealth business. Nevertheless, the large number of M2M protocols currently available hinders the election of a suitable solution that satisfies the requirements that can demand eHealth applications. OBJECTIVES: In the first place, to develop a tool that provides a benchmarking analysis in order to objectively select among the most relevant M2M protocols for eHealth solutions. In the second place, to validate the tool with a particular use case: the respiratory rehabilitation. METHODS: A software tool, called Distributed Computing Framework (DFC), has been designed and developed to execute the benchmarking tests and facilitate the deployment in environments with a large number of machines, with independence of the protocol and performance metrics selected. RESULTS: DDS, MQTT, CoAP, JMS, AMQP and XMPP protocols were evaluated considering different specific performance metrics, including CPU usage, memory usage, bandwidth consumption, latency and jitter. The results obtained allowed to validate a case of use: respiratory rehabilitation of chronic obstructive pulmonary disease (COPD) patients in two scenarios with different types of requirement: Home-Based and Ambulatory. CONCLUSIONS: The results of the benchmark comparison can guide eHealth developers in the choice of M2M technologies. In this regard, the framework presented is a simple and powerful tool for the deployment of benchmark tests under specific environments and conditions.

La salud del ser humano y su armonía con el ambiente

El cuerpo humano se encuentra en un proceso constante de dinamismo y evolución como resultado de su interacción con el ambiente, donde el equilibrio entre órganos y funciones se modifica como consecuencia del cambio en el medio externo, ocasionando la aparición de enfermedades relacionadas con factores físicos, químicos y biológicos. La salud de las personas depende de su capacidad de crear una relación armoniosa con el ambiente, por este motivo no solo se debe tener en cuenta el efecto que los agentes ambientales puedan generar sobre la salud sino también las acciones que el individuo realiza para mantener la integridad de estos ambientes naturales. La salud individual está claramente ligada a la salud de la comunidad y el entorno donde una persona vive, trabaja o se divierte. Los peligros ambientales de gran escala y alcance mundial que amenazan la salud humana comprenden el cambio climático, el agotamiento de la capa estratosférica de ozono, la pérdida de diversidad biológica, cambios en los sistemas hidrológicos y en las reservas de agua dulce, la degradación de la tierra y las presiones ejercidas sobre los sistemas de producción de alimentos. Para apreciar esta escala y el tipo de influencia en la salud humana se requiere una nueva perspectiva concentrada en los ecosistemas y reconocer que el fundamento de una buena salud en las poblaciones depende en gran parte de la estabilidad que puedan conservar los sistemas que mantienen la vida en la biosfera. El objetivo de éste artículo es concientizarnos de la relación que debe existir entre ambiente y salud, y buscar mecanismos que nos permitan evaluar, y prevenir cualquier factor ambiental capaz de afectar adversamente la calidad de vida de las comunidades actuales y futuras.

The human body is in a constant process of dynamism and evolution as a result of its interaction with the environment, where the balance between organs and functions is modified as a consequence of the change in the external environment, causing the appearance of diseases related to physical, chemical and biological. The health of people depends on their ability to create a harmonious relationship with the environment, for this reason not only must take into account the effect that environmental agents can generate on health but also the actions that the individual performs to maintain the Integrity of these natural environments. Individual health is clearly linked to the health of the community and the environment where a person lives, works or has fun. Large-scale, global-scale environmental hazards that threaten human health include climate change, depletion of stratospheric ozone layer, loss of biological diversity, changes in hydrological systems and freshwater reserves, degradation of land and the pressures exerted on food production systems. To appreciate this scale and the type of influence on human health requires a new perspective focused on ecosystems and recognize that the foundation of good health in populations depends to a large extent on the stability that systems that maintain life in the biosphere. The objective of this article is to raise awareness of the relationship between environment and health, and to seek mechanisms that allow us to evaluate and prevent any environmental factors capable of adversely affecting the quality of life of current and future communities.

O corpo humano está em constante processo de dinamismo e evolução como resultado de sua interação com o meio ambiente, onde o equilíbrio entre órgãos e funções é modificado como conseqüência da mudança no ambiente externo, causando o aparecimento de doenças doenças relacionadas com fatores biológicos, físicos e químicos. A saúde das pessoas depende da sua capacidade de criar uma relação harmoniosa com o meio ambiente, por isso não só deve levar em conta o efeito que os agentes ambientais podem gerar na saúde, mas também as ações que o indivíduo realiza para manter a Integridade desses recursos naturais Ambientes. A saúde individual está claramente ligada à saúde da comunidade e do ambiente onde uma pessoa vive, trabalha ou se diverte. Os riscos ambientais em larga escala e em escala global que ameaçam a saúde humana incluem as alterações climáticas, o esgotamento da camada de ozono estratosférico, a perda da diversidade biológica, as alterações nos sistemas hidrológicos e as reservas de água doce, a degradação das terras e as pressões exercidas sobre os sistemas de produção alimentar. Apreciar esta escala e o tipo de influência na saúde humana requer uma nova perspectiva focada nos ecossistemas e reconhecer que o alicerce de uma boa saúde nas populações depende em grande medida da estabilidade dos sistemas que mantêm a vida na biosfera. O objetivo deste artigo é conscientizar a relação entre meio ambiente e saúde e buscar mecanismos que permitam avaliar e prevenir fatores ambientais que possam afetar negativamente a qualidade de vida das comunidades atuais e futuras.

Measurement Issues in Galvanic Intrabody Communication: Influence of Experimental Setup.

SIGNIFICANCE: The need for increasingly energy-efficient and miniaturized bio-devices for ubiquitous health monitoring has paved the way for considerable advances in the investigation of techniques such as intrabody communication (IBC), which uses human tissues as a transmission medium. However, IBC still poses technical challenges regarding the measurement of the actual gain through the human body. The heterogeneity of experimental setups and conditions used together with the inherent uncertainty caused by the human body make the measurement process even more difficult. GOAL: The objective of this study, focused on galvanic coupling IBC, is to study the influence of different measurement equipments and conditions on the IBC channel. METHODS: Different experimental setups have been proposed in order to analyze key issues such as grounding, load resistance, type of measurement device and effect of cables. In order to avoid the uncertainty caused by the human body, an IBC electric circuit phantom mimicking both human bioimpedance and gain has been designed. Given the low-frequency operation of galvanic coupling, a frequency range between 10 kHz and 1 MHz has been selected. RESULTS: The correspondence between simulated and experimental results obtained with the electric phantom have allowed us to discriminate the effects caused by the measurement equipment. CONCLUSION: This study has helped us obtain useful considerations about optimal setups for galvanic-type IBC as well as to identify some of the main causes of discrepancy in the literature.

How technology is empowering patients? A literature review.

BACKGROUND: The term 'Patient Empowerment' (PE) is a growing concept ­ so in popularity as in application ­ covering situations where citizens are encouraged to take an active role in the management of their own health. This concept is serving as engine power for increasing the quality of health systems, but a question is still unanswered, 'how PE will be effectively achieved?' Beyond psychological implications, empowerment of patients in daily practice relies on technology and the way it is used. Unfortunately, the heterogeneity of approaches and technologies makes difficult to have a global vision of how PE is being performed. OBJECTIVE: To clarify how technology is being applied for enhancing patient empowerment as well as to identify current (and future) trends and milestones in this issue. SEARCH STRATEGY: Searches for relevant English language articles using Medline, Scopus, ACM Digital Library, Springer Link, EBSCO host and ScienceDirect databases from the year 2000 until October 2012 were conducted. Among others, a selection criterion was to review articles including terms 'patient' and 'empowerment' in title, abstract or as keywords. MAIN RESULTS AND CONCLUSIONS: Results state that practical approaches to empower patients vary in scope, aim and technology. Health literacy of patients, remote access to health services, and self-care mechanisms are the most valued ways to accomplish PE. Current technology already allows establishing the first steps in the road ahead, but a change of attitude by all stakeholders (i.e. professionals, patients, policy makers, etc.) is required.

A distributed approach to alarm management in chronic kidney disease.

This paper presents the feasibility study of using a distributed approach for the management of alarms from chronic kidney disease patients. In a first place, the key issues regarding alarm definition, classification, and prioritization according to available normalization efforts are analyzed for the main scenarios addressed in hemodialysis. Then, the middleware proposed for alarm management is described, which follows the publish/subscribe pattern, and supports the Object Management Group data distribution service (DDS) standard. This standard facilitates the real-time monitoring of the exchanged information, as well as the scalability and interoperability of the solution developed regarding the different stakeholders and resources involved. Finally, the results section shows, through the proof of concept studied, the viability of DDS for the activation of emergency protocols in terms of alarm prioritization and personalization, as well as some remarks about security, privacy, and real-time communication performance.

Improvement of the Rett syndrome phenotype in a MeCP2 mouse model upon treatment with levodopa and a dopa-decarboxylase inhibitor.

Rett Syndrome is a neurodevelopmental autism spectrum disorder caused by mutations in the gene coding for methyl CpG-binding protein (MeCP2). The disease is characterized by abnormal motor, respiratory, cognitive impairment, and autistic-like behaviors. No effective treatment of the disorder is available. Mecp2 knockout mice have a range of physiological and neurological abnormalities that resemble the human syndrome and can be used as a model to interrogate new therapies. Herein, we show that the combined administration of Levodopa and a Dopa-decarboxylase inhibitor in RTT mouse models is well tolerated, diminishes RTT-associated symptoms, and increases life span. The amelioration of RTT symptomatology is particularly significant in those features controlled by the dopaminergic pathway in the nigrostratium, such as mobility, tremor, and breathing. Most important, the improvement of the RTT phenotype upon use of the combined treatment is reflected at the cellular level by the development of neuronal dendritic growth. However, much work is required to extend the duration of the benefit of the described preclinical treatment.

Galvanic coupling transmission in intrabody communication: a finite element approach.

Galvanic coupling in intrabody communication (IBC) is a technique that couples low-power and low-frequency voltages and currents into the human body, which acts as a transmission medium, and thus constitutes a promising approach in the design of personal health devices. Despite important advances being made during recent years, the investigation of relevant galvanic IBC parameters, including the influence of human tissues and different electrode configurations, still requires further research efforts. The objective of this work is to disclose knowledge into IBC galvanic coupling transmission mechanisms by using a realistic 3-D finite element model of the human arm. Unlike other computational models for IBC, we have modeled the differential configuration of the galvanic coupling as a four-port network in order to analyze the electric field distribution and current density through different tissues. This has allowed us to provide an insight into signal transmission paths through the human body, showing them to be considerably dependent on variables such as frequency and inter-electrode distance. In addition, other important variables, for example bioimpedance and pathloss, have also been analyzed. Finally, experimental measurements were also carried out for the sake of validation, demonstrating the reliability of the model to emulate in general forms some of the behaviors observed in practice.

Dysregulation of the long non-coding RNA transcriptome in a Rett syndrome mouse model.

Mecp2 is a transcriptional repressor protein that is mutated in Rett syndrome, a neurodevelopmental disorder that is the second most common cause of mental retardation in women. It has been shown that the loss of the Mecp2 protein in Rett syndrome cells alters the transcriptional silencing of coding genes and microRNAs. Herein, we have studied the impact of Mecp2 impairment in a Rett syndrome mouse model on the global transcriptional patterns of long non-coding RNAs (lncRNAs). Using a microarray platform that assesses 41,232 unique lncRNA transcripts, we have identified the aberrant lncRNA transcriptome that is present in the brain of Rett syndrome mice. The study of the most relevant lncRNAs altered in the assay highlighted the upregulation of the AK081227 and AK087060 transcripts in Mecp2-null mice brains. Chromatin immunoprecipitation demonstrated the Mecp2 occupancy in the 5'-end genomic loci of the described lncRNAs and its absence in Rett syndrome mice. Most importantly, we were able to show that the overexpression of AK081227 mediated by the Mecp2 loss was associated with the downregulation of its host coding protein gene, the gamma-aminobutyric acid receptor subunit Rho 2 (Gabrr2). Overall, our findings indicate that the transcriptional dysregulation of lncRNAs upon Mecp2 loss contributes to the neurological phenotype of Rett syndrome and highlights the complex interaction between ncRNAs and coding-RNAs.

Survival and factors predicting mortality in hemodialysis patients over 75 years old.

BACKGROUND: Patients starting dialysis treatments are increasingly elderly and with high morbidity and mortality. Survival and factors influencing mortality are discussed. METHODS: We studied 2,601 patients who started hemodialysis in Andalucía (Spain) between 2004 and 2007. Of these, 71 patients died in the first 90 days of hemodialysis treatment and were excluded. Three groups were considered: group A, 694 patients aged less than 60 years; group B, 1,203 patients between 60 and 75 years; and group C, 704 patients aged over 75. Survival and factors associated with mortality were studied. RESULTS: Mean survival was 46 months in group A, 41.6 in group B and 35 in the very elderly group. In univariate analysis using the Cox proportional hazards model, survival in the very elderly patients was significantly influenced by low body mass index (BMI), venous catheter as initial vascular access, arterial hypertension, congestive heart failure (CHF), late referral to nephrologist (<6 months), C-reactive protein (CRP) >10 mg/dL, serum albumin <3.5 g/dL, Kt/V (Daugirdas) <1.2 and time of dialysis session <180 minutes. In multivariate analysis, BMI, CHF, CRP, low serum albumin, Kt/V and time of dialysis session remained as independent predictors of mortality. CONCLUSIONS: Survival of the very elderly patients who remained on hemodialysis more than 90 consecutive days was poor (about 3 years). Heart failure and malnutrition/inflammation are prognostic factors related to mortality in these patients on chronic hemodialysis.

SoM: a smart sensor for human activity monitoring and assisted healthy ageing.

This paper presents the hardware and software design and implementation of a low-cost, wearable, and unobstructive intelligent accelerometer sensor for the monitoring of human physical activities. In order to promote healthy lifestyles to elders for an active, independent, and healthy ageing, as well as for the early detection of psychomotor abnormalities, the activity monitoring is performed in a holistic manner in the same device through different approaches: 1) a classification of the level of activity that allows to establish patterns of behavior; 2) a daily activity living classifier that is able to distinguish activities such as climbing or descending stairs using a simple method to decouple the gravitational acceleration components of the motion components; and 3) an estimation of metabolic expenditure independent of the activity performed and the anthropometric characteristics of the user. Experimental results have demonstrated the feasibility of the prototype and the proposed algorithms.